Biomimetic Total Synthesis of Sarglamides A, B, C, Unnatural-Natural Sarglamide G, and Their Enantiomers

Herein, we report the first biomimetic asymmetric total synthesis of sarglamides A, B, and C, recently isolated from a shrub of the genus Sarcandra. Our synthesis features an efficient one-step intermolecular [4 + 2] Diels-Alder cycloaddition between (S)-α-phellandrene and both enantiomers of toussaintine C, which proceeds with endo-selectivity to give these 6/6/6/5 tetracyclic structures comprising seven stereogenic centers. By this approach, we also elaborated a sarglamide that had not been isolated, which we named sarglamide G. It resulted from the Diels-Alder reaction of (S)-α-phellandrene with (R,R)-toussaintine C via an endo-ortho transition state. Importantly, our study provides the shortest route to this family of unique indolidinoid-monoterpenoid hybrids as well as strong evidence to support their putative biosynthesis.